Dosing & Uses
Dosage Forms & Strengths
tablet (Samsca)
- 15mg
- 30mg
tablet (Jynarque)
- 15mg
- 30mg
- 45mg
- 60mg
- 90mg
Hyponatremia
Samsca only
Indicated for adults with clinically significant euvolemic or hypervolemic hyponatremia (serum sodium <125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction), including patients with heart failure, cirrhosis, and SIADH
Initial: 15 mg PO qDay
Maintenance: May increase to 30 mg qDay after at least 24 hr to achieve the optimal serum sodium level; not to exceed 60 mg/day
Not to exceed 30 days of treatment
Polycystic Kidney Disease
Jynarque only
Indicated to slow kidney function decline in adults at risk of rapidly progressing autosomal dominant polycystic kidney disease (ADPKD)
Initial: 45 mg PO taken on waking and 15 mg taken 8 hr later (ie, 60 mg/day)
Titrate to 60 mg plus 30 mg, then to 90 mg plus 30 mg per day if tolerated, with at least weekly intervals between titrations
Patients may down-titrate based on tolerability
Encourage patients to drink enough water to avoid thirst or dehydration
Dosage Modifications
Renal impairment
- CrCl 10-79 mL/min: No dosage adjustment required
- CrCl <10 mL or dialysis: Not recommended; drug effects on serum sodium levels are likely lost at very low levels of renal function
- Anuria: Contraindicated; no benefit expected
Hepatic impairment
- Moderate and severe hepatic impairment do not affect exposure to tolvaptan to a clinically relevant extent
- Underlying liver disease: Avoid use
Strong CYP3A inhibitors
- Coadministration with strong CYP3A inhibitors: Contraindicated; causes a marked (5-fold) increase in tolvaptan exposure
Moderate CYP3A inhibitors (Samsca)
- Not studied; prescribing information recommends avoiding coadministration
Moderate CYP3A inhibitors (Jynarque)
- Reduce the dose if coadministered with moderate CYP3A inhibitor; consider further reductions if patients cannot tolerate the reduced dose
- Interrupt temporarily for short-term therapy with moderate CYP3A inhibitors if the recommended reduced doses are not available
Dose reduction with moderate CYP3A inhibitors
- Taking 90 mg and 30 mg: Reduce to 45 mg and 15 mg
- Taking 60 mg and 30 mg: Reduce to 30 mg and 15 mg
- Taking 45 mg and 15 mg: Reduce to 15 mg and 15 mg
Potent CYP3A inducers
- Coadministration with potent CYP3A inducers: Monitor and adjust tolvaptan dose accordingly; potent inducers reduce tolvaptan plasma concentrations by 85%
P-gp inhibitors
- Coadministration with P-gp inhibitors: Monitor; tolvaptan dose may need to be reduced
Dosing Considerations
Limitations of use (Samsca)
- Patients should be hospitalized for initiation and reinitiation of therapy to evaluate the therapeutic response and because too-rapid correction of hyponatremia can cause osmotic demyelination
- Do not use in patients requiring intervention to raise serum sodium urgently to prevent or to treat serious neurological symptoms
- It has not been established that raising serum sodium with tolvaptan provides a symptomatic benefit to patients
- Monitor serum sodium
Jynarque
Monitoring to mitigate risk of liver injury
- Perform blood testing for ALT, AST, and bilirubin prior to initiating, at 2 and 4 weeks after initiation, monthly for 18 months, and q3Months thereafter
- Monitor for concurrent symptoms that may indicate liver injury
Safety and efficacy not established
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Contraindicated (2)
- itraconazole
itraconazole will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Larger doses of strong CYP3A4 inhibitors may produce larger increases in tolvaptan exposure. Concomitant use of tolvaptan with strong CYP3A4 inhibitors is contraindicated.
- nirmatrelvir/ritonavir
nirmatrelvir/ritonavir will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Nirmatrelvir/ritonavir is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated concentrations are associated with serious and/or life-threatening reactions. May increase risk of dehydration, hypovolemia, and hyperkalemia associated with tolvaptan.
Serious - Use Alternative (99)
- amobarbital
amobarbital will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- apalutamide
apalutamide will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.
- aprepitant
aprepitant will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- armodafinil
armodafinil will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- artemether/lumefantrine
artemether/lumefantrine will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- atazanavir
atazanavir will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- bosentan
bosentan will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- bosutinib
tolvaptan increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- budesonide
budesonide will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- butabarbital
butabarbital will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- butalbital
butalbital will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- carbamazepine
carbamazepine will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ceritinib
ceritinib will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- chloramphenicol
chloramphenicol will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- cimetidine
cimetidine will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- clarithromycin
clarithromycin will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- cobicistat
cobicistat will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- conivaptan
conivaptan will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- cortisone
cortisone will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- cyclosporine
cyclosporine will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- dabrafenib
dabrafenib will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- darifenacin
darifenacin will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- darunavir
darunavir will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- dasatinib
dasatinib will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- dexamethasone
dexamethasone will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- DHEA, herbal
DHEA, herbal will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- diltiazem
diltiazem will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. In patients taking concomitant moderate CYP3A inhibitors, reduce tolvaptan dose (see Prescribing Information). Consider further reductions if patients cannot tolerate the reduced dose. Interrupt tolvaptan temporarily for short term therapy with moderate CYP3A inhibitors if the recommended reduced doses are not available.
- dronedarone
dronedarone will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- efavirenz
efavirenz will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- enzalutamide
enzalutamide will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- erdafitinib
erdafitinib will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If coadministration unavoidable, separate administration by at least 6 hr before or after administration of P-gp substrates with narrow therapeutic index.
- erythromycin base
erythromycin base will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- erythromycin ethylsuccinate
erythromycin ethylsuccinate will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- erythromycin lactobionate
erythromycin lactobionate will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- erythromycin stearate
erythromycin stearate will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- eslicarbazepine acetate
eslicarbazepine acetate will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- etravirine
etravirine will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- fexinidazole
fexinidazole will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.
- fluconazole
fluconazole will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- fludrocortisone
fludrocortisone will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- fluvoxamine
fluvoxamine will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- fosamprenavir
fosamprenavir will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- fosaprepitant
fosaprepitant will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- fosphenytoin
fosphenytoin will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- grapefruit
grapefruit will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- griseofulvin
griseofulvin will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- hydrocortisone
hydrocortisone will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- idelalisib
idelalisib will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates
- indinavir
indinavir will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- isoniazid
isoniazid will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ivosidenib
ivosidenib will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.
- ketoconazole
ketoconazole will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- lapatinib
lapatinib will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- lasmiditan
lasmiditan increases levels of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- levoketoconazole
levoketoconazole will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- lonafarnib
lonafarnib will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.
- lopinavir
lopinavir will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- lumefantrine
lumefantrine will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- marijuana
marijuana will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- methylprednisolone
methylprednisolone will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- metronidazole
metronidazole will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- miconazole vaginal
miconazole vaginal will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- mifepristone
mifepristone will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- nafcillin
nafcillin will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- nefazodone
nefazodone will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- nelfinavir
nelfinavir will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- nevirapine
nevirapine will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- nifedipine
nifedipine will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- nilotinib
nilotinib will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- oxcarbazepine
oxcarbazepine will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- pentobarbital
pentobarbital will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- phenobarbital
phenobarbital will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- phenytoin
phenytoin will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- pomalidomide
tolvaptan increases levels of pomalidomide by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- posaconazole
posaconazole will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- prednisone
prednisone will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- primidone
primidone will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- quinidine
quinidine will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- quinupristin/dalfopristin
quinupristin/dalfopristin will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ribociclib
ribociclib will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- rifabutin
rifabutin will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- rifampin
rifampin will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- rifapentine
rifapentine will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- ritonavir
ritonavir will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- rufinamide
rufinamide will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- saquinavir
saquinavir will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- secobarbital
secobarbital will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- sotorasib
sotorasib will decrease the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications.
- St John's Wort
St John's Wort will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- tepotinib
tepotinib will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If concomitant use unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.
- tipranavir
tipranavir will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- topiramate
topiramate will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- topotecan
tolvaptan will increase the level or effect of topotecan by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Product labeling for PO topotecan recommends avoiding concomitant use of P-gp inhibitors; the interaction with IV topotecan may be less severe but is still likely of clinical significance
- triamcinolone acetonide injectable suspension
triamcinolone acetonide injectable suspension will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- tucatinib
tucatinib will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.
- verapamil
verapamil will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- voriconazole
voriconazole will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- voxelotor
voxelotor will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.
- zafirlukast
zafirlukast will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
Monitor Closely (195)
- acebutolol
acebutolol and tolvaptan both increase serum potassium. Use Caution/Monitor.
- aceclofenac
aceclofenac and tolvaptan both increase serum potassium. Use Caution/Monitor.
- acemetacin
acemetacin and tolvaptan both increase serum potassium. Use Caution/Monitor.
- albuterol
tolvaptan increases and albuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- amikacin
tolvaptan will increase the level or effect of amikacin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- amiloride
amiloride and tolvaptan both increase serum potassium. Modify Therapy/Monitor Closely.
- amiodarone
amiodarone will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- amitriptyline
tolvaptan will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- arformoterol
tolvaptan increases and arformoterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- aspirin
aspirin and tolvaptan both increase serum potassium. Use Caution/Monitor.
- aspirin rectal
aspirin rectal and tolvaptan both increase serum potassium. Use Caution/Monitor.
- aspirin/citric acid/sodium bicarbonate
aspirin/citric acid/sodium bicarbonate and tolvaptan both increase serum potassium. Use Caution/Monitor.
- atenolol
atenolol and tolvaptan both increase serum potassium. Use Caution/Monitor.
- atorvastatin
atorvastatin will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
tolvaptan will increase the level or effect of atorvastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - azithromycin
azithromycin will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- bazedoxifene/conjugated estrogens
tolvaptan will increase the level or effect of bazedoxifene/conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- bendroflumethiazide
tolvaptan increases and bendroflumethiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- berotralstat
berotralstat will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.
- betaxolol
betaxolol and tolvaptan both increase serum potassium. Use Caution/Monitor.
- bisoprolol
bisoprolol and tolvaptan both increase serum potassium. Use Caution/Monitor.
- bosutinib
bosutinib increases levels of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- budesonide
tolvaptan will increase the level or effect of budesonide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- bumetanide
tolvaptan increases and bumetanide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- candesartan
candesartan and tolvaptan both increase serum potassium. Use Caution/Monitor.
- captopril
tolvaptan, captopril. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hyperkalemia.
- carbenoxolone
tolvaptan increases and carbenoxolone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- carvedilol
carvedilol and tolvaptan both increase serum potassium. Use Caution/Monitor.
- celecoxib
celecoxib and tolvaptan both increase serum potassium. Use Caution/Monitor.
- celiprolol
celiprolol and tolvaptan both increase serum potassium. Use Caution/Monitor.
- chlorothiazide
tolvaptan increases and chlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- chlorthalidone
tolvaptan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- choline magnesium trisalicylate
choline magnesium trisalicylate and tolvaptan both increase serum potassium. Use Caution/Monitor.
- clarithromycin
clarithromycin will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- clotrimazole
clotrimazole will decrease the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- conjugated estrogens
tolvaptan will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- conjugated estrogens, vaginal
tolvaptan will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- cortisone
tolvaptan will increase the level or effect of cortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- crizotinib
crizotinib increases levels of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- cyclopenthiazide
tolvaptan increases and cyclopenthiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- cyclosporine
cyclosporine will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
tolvaptan will increase the level or effect of cyclosporine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - deferasirox
deferasirox will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- deflazacort
tolvaptan will increase the level or effect of deflazacort by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- dexamethasone
tolvaptan will increase the level or effect of dexamethasone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- diclofenac
diclofenac and tolvaptan both increase serum potassium. Use Caution/Monitor.
- diflunisal
diflunisal and tolvaptan both increase serum potassium. Use Caution/Monitor.
- digoxin
tolvaptan will increase the level or effect of digoxin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
digoxin and tolvaptan both increase serum potassium. Use Caution/Monitor. - dobutamine
tolvaptan increases and dobutamine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- docetaxel
tolvaptan will increase the level or effect of docetaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- dopexamine
tolvaptan increases and dopexamine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dronedarone
dronedarone will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- drospirenone
drospirenone and tolvaptan both increase serum potassium. Modify Therapy/Monitor Closely.
- elagolix
elagolix will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
elagolix decreases levels of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed. - eliglustat
eliglustat increases levels of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the P-gp substrate and titrate to clinical effect.
- encorafenib
encorafenib, tolvaptan. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.
- ephedrine
tolvaptan increases and ephedrine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- epinephrine
tolvaptan increases and epinephrine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- epinephrine racemic
tolvaptan increases and epinephrine racemic decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- eprosartan
eprosartan and tolvaptan both increase serum potassium. Use Caution/Monitor.
- erythromycin base
erythromycin base will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- erythromycin ethylsuccinate
erythromycin ethylsuccinate will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- erythromycin lactobionate
erythromycin lactobionate will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- erythromycin stearate
erythromycin stearate will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- esmolol
esmolol and tolvaptan both increase serum potassium. Use Caution/Monitor.
- estradiol
tolvaptan will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- estrogens conjugated synthetic
tolvaptan will increase the level or effect of estrogens conjugated synthetic by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- estrogens esterified
tolvaptan will increase the level or effect of estrogens esterified by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- estropipate
tolvaptan will increase the level or effect of estropipate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- ethacrynic acid
tolvaptan increases and ethacrynic acid decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- etodolac
etodolac and tolvaptan both increase serum potassium. Use Caution/Monitor.
- felodipine
felodipine will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- fenoprofen
fenoprofen and tolvaptan both increase serum potassium. Use Caution/Monitor.
- fludrocortisone
tolvaptan will increase the level or effect of fludrocortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- flurbiprofen
flurbiprofen and tolvaptan both increase serum potassium. Use Caution/Monitor.
- formoterol
tolvaptan increases and formoterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- fosphenytoin
fosphenytoin will decrease the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- furosemide
tolvaptan increases and furosemide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- gentamicin
tolvaptan will increase the level or effect of gentamicin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
tolvaptan increases and gentamicin decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. - glecaprevir/pibrentasvir
glecaprevir/pibrentasvir will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- hydrochlorothiazide
tolvaptan increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- hydrocortisone
tolvaptan will increase the level or effect of hydrocortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- ibuprofen
ibuprofen and tolvaptan both increase serum potassium. Use Caution/Monitor.
- ibuprofen IV
ibuprofen IV and tolvaptan both increase serum potassium. Use Caution/Monitor.
- indapamide
tolvaptan increases and indapamide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- indinavir
indinavir will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
tolvaptan will increase the level or effect of indinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - indomethacin
indomethacin and tolvaptan both increase serum potassium. Use Caution/Monitor.
- irbesartan
irbesartan and tolvaptan both increase serum potassium. Use Caution/Monitor.
- irinotecan liposomal
tolvaptan will increase the level or effect of irinotecan liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- isoproterenol
tolvaptan increases and isoproterenol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- istradefylline
istradefylline will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.
istradefylline will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates. - itraconazole
tolvaptan will increase the level or effect of itraconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- ivacaftor
ivacaftor increases levels of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.
- ivermectin
tolvaptan will increase the level or effect of ivermectin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- ketoconazole
ketoconazole will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- ketoprofen
ketoprofen and tolvaptan both increase serum potassium. Use Caution/Monitor.
- ketorolac
ketorolac and tolvaptan both increase serum potassium. Use Caution/Monitor.
- ketorolac intranasal
ketorolac intranasal and tolvaptan both increase serum potassium. Use Caution/Monitor.
- labetalol
labetalol and tolvaptan both increase serum potassium. Use Caution/Monitor.
- lapatinib
lapatinib will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- lenacapavir
lenacapavir will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.
- levalbuterol
tolvaptan increases and levalbuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- levoketoconazole
levoketoconazole will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- lomitapide
lomitapide increases levels of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing dose when used concomitantly with lomitapide.
- lonafarnib
lonafarnib will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Lonafarnib is a weak P-gp inhibitor. Monitor for adverse reactions if coadministered with P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities. Reduce P-gp substrate dose if needed.
- loperamide
tolvaptan will increase the level or effect of loperamide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- loratadine
loratadine will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- lorlatinib
lorlatinib will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- lornoxicam
lornoxicam and tolvaptan both increase serum potassium. Use Caution/Monitor.
- losartan
losartan and tolvaptan both increase serum potassium. Use Caution/Monitor.
- lovastatin
lovastatin will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
tolvaptan will increase the level or effect of lovastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - maraviroc
tolvaptan will increase the level or effect of maraviroc by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- meclofenamate
meclofenamate and tolvaptan both increase serum potassium. Use Caution/Monitor.
- mefenamic acid
mefenamic acid and tolvaptan both increase serum potassium. Use Caution/Monitor.
- meloxicam
meloxicam and tolvaptan both increase serum potassium. Use Caution/Monitor.
- mestranol
tolvaptan will increase the level or effect of mestranol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- metaproterenol
tolvaptan increases and metaproterenol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- methyclothiazide
tolvaptan increases and methyclothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. .
- methylphenidate transdermal
methylphenidate transdermal and tolvaptan both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
- methylprednisolone
tolvaptan will increase the level or effect of methylprednisolone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- metolazone
tolvaptan increases and metolazone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- metoprolol
metoprolol and tolvaptan both increase serum potassium. Use Caution/Monitor.
- mitotane
mitotane decreases levels of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.
- nabumetone
nabumetone and tolvaptan both increase serum potassium. Use Caution/Monitor.
- nadolol
nadolol and tolvaptan both increase serum potassium. Use Caution/Monitor.
- naproxen
naproxen and tolvaptan both increase serum potassium. Use Caution/Monitor.
- nebivolol
nebivolol and tolvaptan both increase serum potassium. Use Caution/Monitor.
- nefazodone
nefazodone will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- nelfinavir
tolvaptan will increase the level or effect of nelfinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- neomycin PO
tolvaptan will increase the level or effect of neomycin PO by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- nicardipine
nicardipine will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- nifedipine
nifedipine will decrease the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- nilotinib
nilotinib will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- norepinephrine
tolvaptan increases and norepinephrine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- olmesartan
olmesartan and tolvaptan both increase serum potassium. Use Caution/Monitor.
- oxaprozin
oxaprozin and tolvaptan both increase serum potassium. Use Caution/Monitor.
- paclitaxel
tolvaptan will increase the level or effect of paclitaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- paclitaxel protein bound
tolvaptan will increase the level or effect of paclitaxel protein bound by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- paliperidone
tolvaptan will increase the level or effect of paliperidone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- parecoxib
parecoxib and tolvaptan both increase serum potassium. Use Caution/Monitor.
- paromomycin
tolvaptan will increase the level or effect of paromomycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- penbutolol
penbutolol and tolvaptan both increase serum potassium. Use Caution/Monitor.
- phenobarbital
phenobarbital will decrease the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- phenytoin
phenytoin will decrease the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- pindolol
pindolol and tolvaptan both increase serum potassium. Use Caution/Monitor.
- pirbuterol
tolvaptan increases and pirbuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- piroxicam
piroxicam and tolvaptan both increase serum potassium. Use Caution/Monitor.
- ponatinib
ponatinib increases levels of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- posaconazole
tolvaptan will increase the level or effect of posaconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- potassium acid phosphate
potassium acid phosphate and tolvaptan both increase serum potassium. Modify Therapy/Monitor Closely.
- potassium chloride
potassium chloride and tolvaptan both increase serum potassium. Modify Therapy/Monitor Closely.
- potassium citrate
potassium citrate and tolvaptan both increase serum potassium. Modify Therapy/Monitor Closely.
- prednisolone
tolvaptan will increase the level or effect of prednisolone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- prednisone
tolvaptan will increase the level or effect of prednisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- propranolol
propranolol and tolvaptan both increase serum potassium. Use Caution/Monitor.
- quercetin
quercetin will decrease the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- ranolazine
ranolazine will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- rifampin
rifampin will decrease the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- risperidone
tolvaptan will increase the level or effect of risperidone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- ritonavir
ritonavir will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
tolvaptan will increase the level or effect of ritonavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - rucaparib
rucaparib will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.
- sacubitril/valsartan
sacubitril/valsartan and tolvaptan both increase serum potassium. Use Caution/Monitor.
- salicylates (non-asa)
salicylates (non-asa) and tolvaptan both increase serum potassium. Use Caution/Monitor.
- salmeterol
tolvaptan increases and salmeterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- salsalate
salsalate and tolvaptan both increase serum potassium. Use Caution/Monitor.
- saquinavir
tolvaptan will increase the level or effect of saquinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- sarecycline
sarecycline will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for toxicities of P-gp substrates that may require dosage reduction when coadministered with P-gp inhibitors.
- silodosin
tolvaptan will increase the level or effect of silodosin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- simvastatin
simvastatin will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- sirolimus
sirolimus will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
tolvaptan will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - sotalol
sotalol and tolvaptan both increase serum potassium. Use Caution/Monitor.
- spironolactone
spironolactone and tolvaptan both increase serum potassium. Modify Therapy/Monitor Closely.
- St John's Wort
St John's Wort will decrease the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- stiripentol
stiripentol, tolvaptan. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.
stiripentol will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing the dose of P-glycoprotein (P-gp) substrates, if adverse reactions are experienced when administered concomitantly with stiripentol. - streptomycin
tolvaptan will increase the level or effect of streptomycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- succinylcholine
succinylcholine and tolvaptan both increase serum potassium. Use Caution/Monitor.
- sulfasalazine
sulfasalazine and tolvaptan both increase serum potassium. Use Caution/Monitor.
- sulindac
sulindac and tolvaptan both increase serum potassium. Use Caution/Monitor.
- tacrolimus
tacrolimus will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
tolvaptan will increase the level or effect of tacrolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - tazemetostat
tazemetostat will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tecovirimat
tecovirimat will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.
- telmisartan
telmisartan and tolvaptan both increase serum potassium. Use Caution/Monitor.
- terbutaline
tolvaptan increases and terbutaline decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- timolol
timolol and tolvaptan both increase serum potassium. Use Caution/Monitor.
- tobramycin
tolvaptan will increase the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- tolfenamic acid
tolfenamic acid and tolvaptan both increase serum potassium. Use Caution/Monitor.
- tolmetin
tolmetin and tolvaptan both increase serum potassium. Use Caution/Monitor.
- torsemide
tolvaptan increases and torsemide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- trazodone
trazodone will decrease the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- triamterene
triamterene and tolvaptan both increase serum potassium. Modify Therapy/Monitor Closely.
- tucatinib
tucatinib will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.
- valsartan
valsartan and tolvaptan both increase serum potassium. Use Caution/Monitor.
- vemurafenib
vemurafenib increases levels of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- verapamil
verapamil will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Coadministration of moderate CYP 3A inhibitors, such as Verapamil with Tolvaptan should be avoided.
- vinblastine
tolvaptan will increase the level or effect of vinblastine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- vincristine
tolvaptan will increase the level or effect of vincristine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- vincristine liposomal
tolvaptan will increase the level or effect of vincristine liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
Minor (11)
- acetazolamide
acetazolamide will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- aliskiren
tolvaptan will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.
- alvimopan
tolvaptan will increase the level or effect of alvimopan by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.
- ambrisentan
tolvaptan will increase the level or effect of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.
- anastrozole
anastrozole will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- armodafinil
tolvaptan will increase the level or effect of armodafinil by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.
- cyclophosphamide
cyclophosphamide will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- fexofenadine
tolvaptan will increase the level or effect of fexofenadine by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.
- larotrectinib
larotrectinib will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- loratadine
tolvaptan will increase the level or effect of loratadine by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.
- noni juice
noni juice and tolvaptan both increase serum potassium. Minor/Significance Unknown.
Adverse Effects
>10%
Samsca
- Nausea (21%)
- Thirst (16%)
- Dry mouth (13%)
- Pollakiuria (4-11%)
- Urinary frequency/output increased (11%)
Jynarque
- Increased urination (69.5%)
- Thirst (63.7%)
- Dry mouth (16%)
- Fatigue (13.6%)
- Diarrhea (13.3%)
- Dizziness (11.3%)
1-10%
Samsca
- GI bleeding with preexisting cirrhosis (10%)
- Weakness (9%)
- Constipation (7%)
- Hyperglycemia (6%)
- Anorexia (4%)
- Pyrexia (4%)
Jynarque
- Dyspepsia (7.9%)
- Decreased appetite (7.2%)
- Abdominal distension (4.9%)
- Dry skin (4.9%)
- Rash (4.2%)
- Hyperuricemia (3.9%)
- Palpitations (3.5%)
Postmarketing Reports
Neurologic: Osmotic demyelination syndrome
Investigations: Hypernatremia
Immune system disorders: Hypersensitivity reactions including anaphylactic shock and rash
Hepatobiliary disorders: Liver failure requiring transplantation
Warnings
Black Box Warnings
Samsca
- Initiate or reinitiate only in a hospital where serum sodium level can be monitored closely
- Too-rapid correction of hyponatremia (eg, >12 mEq/L/24 hr) can cause osmotic demyelination resulting in dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma, and death
- In susceptible patients, including those with severe malnutrition, alcoholism, or advanced liver disease, slower rates of correction may be advisable
- Not for use for ADPKD because of risk of hepatoxicity; tolvaptan (Jynarque) is specifically indicated for ADPKD
Jynarque
- Can cause serious and potentially fatal liver injury; acute liver failure requiring liver transplantation reported
- Measure ALT, AST and bilirubin before initiating treatment, at 2 weeks and 4 weeks after initiation, monthly for the first 18 months ,and q3Months thereafter
- Prompt action in response to laboratory abnormalities, signs, or symptoms indicative of hepatic injury can mitigate, but not eliminate, the risk of serious hepatotoxicity
- Because of the risks of serious liver injury, available only through a restricted distribution program under a Risk Evaluation and Mitigation Strategy (REMS) called the Jynarque REMS Program; additional information is available at www.jynarquerems.com or by telephone at 1-877-726-7220
Contraindications
Concomitant use of strong CYP3A inhibitors
Hypersensitivity (eg, anaphylactic shock, generalized rash)
Anuria
Inability of patient to sense or appropriately respond to thirst
Hypovolemic hyponatremia
Samsca
- Use in patients with ADPKD outside of FDA-approved REMS (see Black Box Warnings)
- Urgent need to raise serum sodium acutely
Jynarque
- History, signs, or symptoms of significant liver impairment or injury; this contraindication does not apply to uncomplicated polycystic liver disease
- Uncorrected abnormal blood sodium concentrations
- Uncorrected urinary outflow obstruction
Cautions
Hypernatremia, hypovolemia, and/or dehydration may occur; encourage patient to drink whenever thirsty
Patients with partial obstruction of urinary outflow, patients with prostatic hypertrophy or impairment of micturition, have increased risk of developing acute retention
Can cause serious and potentially fatal liver injury; acute liver failure requiring liver transplantation reported; discontinue if laboratory abnormalities or signs or symptoms of liver injury are evident (see Black Box Warnings); limit duration of therapy to 30 days; avoid use in patients with underlying liver disease, including cirrhosis, because ability to recover from liver injury may be impaired
In patients who develop medically significant signs or symptoms of hypovolemia, interrupt or discontinue therapy and provide supportive care with careful management of vital signs, fluid balance and electrolytes; fluid restriction during therapy may increase risk of dehydration and hypovolemia; patients receiving therapy should continue ingestion of fluid in response to thirst
Osmotic demyelination syndrome
- Osmotic demyelination syndrome is a risk associated with too-rapid correction of hyponatremia (see Black Box Warnings)
- In susceptible patients, including those with severe malnutrition, alcoholism or advanced liver disease, slower rates of correction may be advisable
- In patients who develop too rapid a rise in serum sodium, discontinue or interrupt treatment and consider administration of hypotonic fluid; fluid restriction during first 24 hr of therapy may increase likelihood of overly-rapid correction of serum sodium, and should generally be avoided; co-administration of diuretics also increases risk of too rapid correction of serum sodium; such patients should undergo close monitoring of serum sodium
- Patients with symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice should discontinue treatment
Drug interaction overview
- Hypertonic saline: Concomitant use not recommended
- Diuretics: Increases risk for dehydration
- P-gp inhibitors: Monitor; dose reduction may be required
- Drugs that increase serum potassium: Tolvaptan may have additive hyperkalemic effects if coadministered
- P-gp substrates: Tolvaptan may increase AUC and Cmax of P-gp substrates
- OATP1B1/3 and OAT3 substrates: Avoid concomitant use; tolvaptan may increase plasma concentrations of these substrates
- BCRP substrates: Avoid concomitant use; tolvaptan is an inhibitor of BCRP
- V2-receptor agonists: Avoid concomitant use; tolvaptan, a V2-antagonist, interferes with V2-agonist activity (eg, desmopressin [dDAVP])
-
CYP3A
- Tolvaptan is a substrate of CYP3A
- CYP3A inhibitors can lead to a marked increase in tolvaptan concentrations
- Coadministration with strong CY3A inhibitors: Contraindicated
- Coadministration with moderate CYP3A inhibitors: Avoid (Samsca); modify dose (Jynarque)
- Coadministration with CYP3A inducers: Monitor; dosage increase may be required
Pregnancy & Lactation
Pregnancy
Available data are insufficient to determine if there is a drug-associated risk of adverse developmental outcomes
Animal studies
- In embryo-fetal development studies, pregnant rats and rabbits received oral tolvaptan during organogenesis
- At maternally nontoxic doses, tolvaptan did not cause any developmental toxicity in rats or in rabbits at exposures approximately 4- and 1-times, respectively, the human exposure at the maximum recommended human dose (MRHD) of 90/30 mg; however, effects on embryo-fetal development occurred in both species at maternally toxic doses
Lactation
Data are not available on the presence of tolvaptan in human milk, the effects on the breastfed infant, or the effects on milk production
Tolvaptan is present in rat milk
Because of the potential for serious adverse reactions, including liver toxicity, electrolyte abnormalities (eg, hypernatremia), hypotension, and volume depletion in breastfed infants, advise women not to breastfeed during treatment
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Selective vasopressin V2-receptor antagonist that causes an increase in urine water excretion that results in an increase in free water clearance (aquaresis), a decrease in urine osmolality, and a resulting increase in serum sodium concentration
Absorption
Absolute bioavailability: Unknown; at least 40% of the dose is absorbed as tolvaptan or metabolites
Peak plasma concentration: 2-4 hr
Distribution
Protein bound: 99%
Vd: 3 L/kg
Metabolism
Eliminated entirely by nonrenal routes and mainly, if not exclusively, metabolized by CYP3A
Elimination
Half-life, terminal: 12 hr
Clearance: 4 mL/min/kg
Excretion: Nonrenal
Administration
Oral Administration
May take with or without food
Samsca
- Do not exceed 30 days of administration to minimize risk of liver injury
- Following discontinuation, advise patient to resume fluid restriction and monitor changes in serum sodium and volume status
Jynarque
- If a dose is not taken at the scheduled time, take the next dose at its scheduled time
Storage
Tablets (Samsca): Store at 15-30°C (59-86°F)
Tablets (Jynarque): Store at 20-25°C (68-77°F), excursions permitted between 15-30°C (59-86°F)
Images
BRAND | FORM. | UNIT PRICE | PILL IMAGE |
---|---|---|---|
tolvaptan oral - | 30 mg tablet | ![]() | |
tolvaptan oral - | 15 mg tablet | ![]() | |
tolvaptan oral - | 30 mg tablet | ![]() | |
Samsca oral - | 30 mg tablet | ![]() | |
Samsca oral - | 15 mg tablet | ![]() |
Copyright © 2010 First DataBank, Inc.
Patient Handout
tolvaptan oral
TOLVAPTAN - ORAL
(tol-VAP-tan)
COMMON BRAND NAME(S): Samsca
WARNING: Treatment with this drug should be started or restarted in a hospital for proper monitoring. If your level of sodium in the blood is raised too quickly, it may cause a serious (even fatal) condition called osmotic demyelination syndrome. The risk is higher if you have liver disease, poor nutrition, or if you use/abuse alcohol. Tell your doctor right away if you have symptoms such as trouble speaking/swallowing, mental/mood changes (such as confusion), weakness/involuntary movement in the arms/legs, or seizures.Do not use this medication to treat a certain kidney problem (autosomal dominant polycystic kidney disease-ADPKD). Due to the risk of serious liver damage, you must be in a special program for you to take this medication to treat ADPKD. Ask your doctor for details.
USES: This medication is used to treat low levels of salt (sodium) in the blood, which can result from conditions such as heart failure and certain hormone imbalances. Tolvaptan belongs to a class of drugs known as vasopressin receptor antagonists. It works by increasing the amount of urine you make, causing your body to get rid of extra water. This helps to slowly increase to normal levels of salt in the blood.Different brands of this medication have different uses. Do not change brands of this medication unless directed by your doctor.
HOW TO USE: Read the Medication Guide provided by your pharmacist before you start using tolvaptan and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Take this medication by mouth with or without food as directed by your doctor, usually once daily. You should not take this medication for longer than 30 days.To prevent dehydration, always have water ready to drink while taking tolvaptan. Drink when you are thirsty unless otherwise directed by your doctor.Use this medication regularly to get the most benefit from it. To help you remember, take it at the same time each day. Do not stop and restart this medication on your own. You may need to go back to a hospital to restart this medication. Tell your doctor right away if you stop taking this medication for any reason.Avoid eating grapefruit or drinking grapefruit juice while using this medication unless your doctor or pharmacist says you may do so safely. Grapefruit can increase the chance of side effects with this medicine. Ask your doctor or pharmacist for more details.The dosage is based on your medical condition and response to treatment.
SIDE EFFECTS: See also Warning section.Thirst, dry mouth, loss of appetite, constipation, or weakness may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Dehydration can occur. The risk is increased if you have vomiting or diarrhea that doesn't stop, and you cannot drink normally. Contact your doctor right away if you notice any symptoms of dehydration, such as fast heartbeat or dizziness/lightheadedness.People with severe liver disease (cirrhosis) may have increased risk of bleeding from the stomach or intestines while taking this medication. Tell your doctor right away if you have any of the following symptoms: black/bloody stools, vomit that contains blood or looks like coffee grounds.Tolvaptan may rarely cause serious (possibly fatal) liver disease. Get medical help right away if you have any symptoms of liver damage, such as: nausea/vomiting that doesn't stop, loss of appetite, stomach/abdominal pain, yellowing eyes/skin, dark urine.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
PRECAUTIONS: Before taking tolvaptan, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: diabetes, liver disease, trouble urinating (such as due to enlarged prostate, blockage, inability to make urine), use/abuse of alcohol.To prevent dehydration while taking this medication, you must be able to replace fluids by drinking. Before taking this medication, tell your doctor if you are not able to drink normally or if you cannot feel if you are thirsty. (See also How to Use section.)This medication may rarely make your blood sugar rise, which can cause or worsen diabetes. If you have diabetes, check your blood sugar regularly as directed and share the results with your doctor. Your doctor may need to adjust your diabetes medication, exercise program, or diet.Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.It is unknown if this medication passes into breast milk. Consult your doctor before breast-feeding.
DRUG INTERACTIONS: See also How to Use section.Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.A product that may interact with this drug is: desmopressin.Other medications can affect the removal of tolvaptan from your body, which may affect how tolvaptan works. Examples include azole antifungals (such as ketoconazole, itraconazole), cobicistat, HIV protease inhibitors (such as lopinavir), macrolide antibiotics (such as clarithromycin, erythromycin), ribociclib, rifamycins (such as rifabutin, rifampin), ritonavir, St. John's wort, drugs used to treat seizures (such as carbamazepine, phenytoin), among others.
OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.
NOTES: Do not share this medication with others.Lab and/or medical tests (such as levels of sodium/potassium in the blood) should be done while you are taking this medication. Keep all medical and lab appointments.
MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.
STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.
Information last revised October 2023. Copyright(c) 2023 First Databank, Inc.
IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.
Formulary
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